SIRT3 protects from hypoxia and staurosporine-mediated cell death by maintaining mitochondrial membrane potential and intracellular pH

Cell Death Differ. 2012 Nov;19(11):1815-25. doi: 10.1038/cdd.2012.62. Epub 2012 May 18.


Mitochondrial sirtuin 3 (SIRT3) mediates cellular resistance toward various forms of stress. Here, we show that in mammalian cells subjected to hypoxia and staurosporine treatment SIRT3 prevents loss of mitochondrial membrane potential (ΔΨ(mt)), intracellular acidification and reactive oxygen species accumulation. Our results indicate that: (i) SIRT3 inhibits mitochondrial permeability transition and loss of membrane potential by preventing HKII binding to the mitochondria, (ii) SIRT3 increases catalytic activity of the mitochondrial carbonic anhydrase VB, thereby preventing intracellular acidification, Bax activation and apoptotic cell death. In conclusion we propose that, in mammalian cells, SIRT3 has a central role in connecting changes in ΔΨ(mt), intracellular pH and mitochondrial-regulated apoptotic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Carbonic Anhydrases / metabolism
  • Cell Hypoxia*
  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology*
  • HeLa Cells
  • Hexokinase / metabolism
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • K562 Cells
  • Membrane Potential, Mitochondrial / drug effects*
  • Mitochondria / metabolism
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism
  • Sirtuin 3 / antagonists & inhibitors
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism*
  • Staurosporine / pharmacology*
  • bcl-2-Associated X Protein / metabolism


  • Enzyme Inhibitors
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Hexokinase
  • Sirtuin 3
  • Carbonic Anhydrases
  • Staurosporine